Next generation neural probe technology must enable neuroscientists to bridge the gap between neurons and neuronal pools to fully understand the orchestrated 'temporal dynamics'of the brain. This will require high-density, stable recordings in longitudinal experiments. Similarly, next generation brain machine interfaces (BMI) must improve longevity and reliability of the recorded neural signals if translation of the research technology to the clinical realm is to be successful. Long-term signal degradation is widely believed to be directly related to cellular reactivity in the presence of the neural probe. The sub-cellular edge electrode array (or "SEE" probe) was designed to mitigate the cellular reactivity evident in conventional microelectrode designs and thereby address the longevity and stability issues of recording technology. The SEE design concept hypothesized that if a structural feature size is smaller than a reactive cell body (<7 <m), the resulting cellular encapsulation would be mitigated by the prevention of cellular spreading or adhesion. This biomimetic concept resulted in the design of a conventional probe shank supporting a thin parylene platform only 5-5m thick. Histology results after 4 weeks show that cellular density surrounding the edge of the thin parylene structure had only a 129 percent increase relative to healthy tissue, versus a 425 percent increase around a conventional probe shank. This study proved that tissue encapsulation could be mitigated by a sub-cellular geometry and the appropriate electrode placement. Since this ground-breaking study, the SEE design concept has been further developed. New preliminary work has provided evidence of electrical stability using a parylene substrate, functional electrode arrays with a multi-sided edge geometry, and the ability to record neural activity in acute preparations. The SEE probe has tremendous promise for both research tools and clinical devices using recording technology. The proposed Phase I project will show the technical merit of the SEE probe through microfabrication and optimization (Aim 1), and providing long-term electrical validation (Aim 2). The scientific merit will be clearly demonstrated in chronic animal studies, which will use electrophysiology, electrode impedance, and histology to compare the edge electrodes to planar electrodes on the same device (Aim 3). NeuroNexus Technologies, a leading supplier of microfabricated, microscale neural probes, and the University of Michigan's Neural Engineering Laboratory, will collaborate to execute this important scientific and translational opportunity. PUBLIC HEALTH RELEVANCE: The primary objective of the proposed work is to develop and validate a microelectrode technology that has shown great promise in improving biocompatibility. This work will microfabricate a novel biomimetic design, the "sub-cellular edge electrode" array, and provide subsequent long-term validation in animal studies. Animal studies are expected to show improved electrophysiological recording quality, stability, and longevity. Such microelectrode technology will enable neuroscientists and clinicians to achieve long-term sensing in the brain, which would greatly improve our understanding of healthy brain function and offer new opportunities for those suffering from neurological disorders such as spinal cord injury, epilepsy, or ALS.